Ultra-short, high-field strength electric pulses may be used in the electroperturbation of biological cells. For example, these electric pulses may be used in treatment of human cells and tissue including tumor cells, such as basal cell carcinoma, squamous cell carcinoma and melanoma. For in detail discussion of such applications, for example, see, Garon et al. “In Vitro and In Vivo Evaluation and a Case Report of Intense Nanosecond Pulsed Electric Field as a Local Therapy for Human Malignancies”, Int. J. Cancer, vol. 121, 2007, pages 675-682.
The voltage induced across a cell membrane may depend on the pulse length and pulse amplitude. Pulses longer than about 1 microsecond may charge the outer cell membrane and lead to opening of pores, either temporarily or permanently. Permanent openings may result in cell death.
Pulses much shorter than about 1 microsecond may affect the cell interior without adversely affecting the outer cell membrane. Such shorter pulses with a field strength varying in the range of 1 MV/m to 10 MV/m may trigger apoptosis or programmed cell death. Higher amplitude and shorter electric pulses are useful in manipulating intracellular structures such as nuclei and mitochondria.
Spark gap switched transmission lines have been used to generate ultra-short pulses. However, they may be physically large and have only a low repetition rate. They may also have only a relatively short lifetime, and provide erratic pulses with a large amount of jitter. The transmission line capacitance may also need to be charged rapidly in order to overvolt the spark gap to meet a fast rise time requirement.
Radio frequency metal-oxide semiconductor field effect transistor (MOSFET) switched capacitors have also been used to generate ultra-short pulses. However, MOSFET switched capacitors may not be able to generate pulses with lengths narrower than 15-20 nanoseconds. This may be due to complications of MOSFET driving circuits and inherent limitations of many MOSFET devices.
Nanosecond high voltage based pulse generators based on diode opening switches have also been proposed for biological and medical applications. For example see: Gundersen et al. “Nanosecond Pulse Generator Using a Fast Recovery Diode”, IEEE 26th Power Modulator Conference, 2004, pages 603-606; Tang et al. “Solid-State High Voltage Nanosecond Pulse Generator,” IEEE Pulsed Power Conference, 2005, pages 1199-1202; Tang et al. “Diode Opening Switch Based Nanosecond High Voltage Pulse Generators for Biological and Medical Applications”, IEEE Transactions on Dielectrics and Electrical Insulation, Vol. 14, No. 4, 2007, pages 878-883; Yampolsky et al., “Repetitive Power Pulse Generator With Fast Rising Pulse” U.S. Pat. No. 6,831,377; Gundersen et al., “Method for Intracellular Modifications Within Living Cells Using Pulsed Electric Fields”, U.S. Patent Publication No. 2006/0062074; Kuthi et al., “High Voltage Nanosecond Pulse Generator Using Fast Recovery Diodes for Cell Electro-Manipulation”, U.S. Patent Publication No. 2007/0031959; and Krishnaswamy et al., “Compact Subnanosecond High Voltage Pulse Generation System for Cell Electro-Manipulation”, U.S. Patent Publication No. 2008/0231337.
The diode opening switches may operate at two different modes. The first mode is called junction recovery (JR) mode and the second mode silicon opening switch (SOS) mode. For in detail description of diode opening switches, for example, see: Moll et al., “Physical Modeling of the Pulse and Harmonic Step Recovery Diode for Generation Circuits”, Proceedings of the IEEE, vol. 57, no. 7, 1969, pages 1250-1259; Hewlett Packard Application Note 918, “Pulse and Waveform Generation with Step Recovery Diodes”; Kotov et al., “A Novel Nanosecond Semiconductor Opening Switch for Megavolt Repetitive Pulsed Power Technology: Experiment and Applications,” Proc. 9th Int. IEEE Pulsed Power Conf., Albuquerque, N. Mex., 1993, pages 134-139; Lyubutin et al., “Repetitive Nanosecond All-Solid-State Pulsers Based on SOS Diodes”, IEEE 11th Intern. Pulsed Power Conf., Baltimore, Md., 1997, pages 992-998; Rukin, “High-Power Nanosecond Pulse Generators Based on Semiconductor Opening Switches”, Instruments and Experimental Techniques, vol. 42, No. 4, 1999, pages 439-467; and Grekhov et al., “Physical Basis for High-Power Semiconductor Nanosecond Opening Switches,” IEEE Transactions on Plasma Science, vol. 28, 2000, pages 1540-1544.